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Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants

Genevieve G Fouda1, Tatenda Mahlokozera1, Jesus F Salazar-Gonzalez2, Maria G Salazar2, Gerald Learn3, Surender B Kumar4, S Moses Dennison1, Elizabeth Russell56, Katherine Rizzolo7, Frederick Jaeger1, Fangping Cai1, Nathan A Vandergrift1, Feng Gao1, Beatrice Hahn3, George M Shaw3, Christina Ochsenbauer2, Ronald Swanstrom56, Steve Meshnick56, Victor Mwapasa8, Linda Kalilani8, Susan Fiscus56, David Montefiori1, Barton Haynes1, Jesse Kwiek4, S Munir Alam1 and Sallie R Permar1*

Author Affiliations

1 Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA

2 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

3 Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

4 Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA

5 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA

6 Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA

7 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA, USA

8 Department of Community Health, University of Malawi, Blantyre, Malawi

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Retrovirology 2013, 10:3  doi:10.1186/1742-4690-10-3

Published: 10 January 2013

Abstract

Background

Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmitted variants, genetic or phenotypic properties of the virus Envelope (Env) could be important for the establishment of infant infection. We examined the efficiency of virologic functions required for initiation of infection in the gastrointestinal tract and the neutralization sensitivity of HIV-1 Env variants isolated from milk of three postnatally-transmitting mothers (n=13 viruses), five clinically-matched nontransmitting mothers (n=16 viruses), and seven postnatally-infected infants (n = 7 postnatally-transmitted/founder (T/F) viruses).

Results

There was no difference in the efficiency of epithelial cell interactions between Env virus variants from the breast milk of transmitting and nontransmitting mothers. Moreover, there was similar efficiency of DC-mediated trans-infection, CCR5-usage, target cell fusion, and infectivity between HIV-1 Env-pseudoviruses from nontransmitting mothers and postnatal T/F viruses. Milk Env-pseudoviruses were generally sensitive to neutralization by autologous maternal plasma and resistant to breast milk neutralization. Infant T/F Env-pseudoviruses were equally sensitive to neutralization by broadly-neutralizing monoclonal and polyclonal antibodies as compared to nontransmitted breast milk Env variants.

Conclusion

Postnatally-T/F Env variants do not appear to possess a superior ability to interact with and cross a mucosal barrier or an exceptional resistance to neutralization that define their capability to initiate infection across the infant gastrointestinal tract in the setting of preexisting maternal antibodies.

Keywords:
HIV; Mother to child transmission; Galcer; Dendritic cells; Neutralizing antibodies